Will kinase inhibitors make it as glioblastoma drugs? Journal Article
| Authors: | Mellinghoff, I. K.; Schultz, N.; Mischel, P. S.; Cloughesy, T. F. |
| Article Title: | Will kinase inhibitors make it as glioblastoma drugs? |
| Abstract: | Kinase inhibitors have emerged as effective cancer therapeutics in a variety of human cancers. Glioblastoma (GBM), the most common malignant brain tumor in adults, represents a compelling disease for kinase inhibitor therapy because the majority of these tumors harbor genetic alterations that result in aberrant activation of growth factor signaling pathways. Attempts to target the Ras - Phosphatidylinositol 3-kinase (PI3K) - mammalian Target of Rapamycin (mTOR) axis in GBM with first generation receptor tyrosine kinase (RTK) inhibitors and rapalogs have been disappointing. However, there is reason for renewed optimism given the now very detailed knowledge of the cancer genome in GBM and a wealth of novel compounds entering the clinic, including next generation RTK inhibitors, class I PI3K inhibitors, mTOR kinase inhibitors (TORKinibs), and dual PI3(K)/mTOR inhibitors. This chapter reviews common genetic alterations in growth factor signaling pathways in GBM, their validation as therapeutic targets in this disease, and strategies for future clinical development of kinase inhibitors for high grade glioma. © 2012 Springer-Verlag Berlin Heidelberg. |
| Keywords: | somatic mutation; frameshift mutation; missense mutation; erlotinib; nonhuman; temozolomide; glioma; gene; imatinib; breast cancer; gene amplification; epidermal growth factor receptor; tumor regression; platelet derived growth factor receptor; chronic myeloid leukemia; phosphatidylinositol 3 kinase; oncogene h ras; cancer resistance; protein tyrosine kinase inhibitor; tumor recurrence; glioblastoma; medulloblastoma; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; carcinogenicity; gefitinib; neurofibromin; ependymoma; oligodendroglioma; drug blood level; oncogene k ras; trastuzumab; drug tumor level; astrocytoma; b raf kinase; rapamycin; pik3ca gene; nonsense mutation; penetrance; braf gene; antiproliferative activity; oncogene n ras; pilocytic astrocytoma; crizotinib; met gene; nf1 gene; gain of function mutation; pik3r1 gene |
| Journal Title: | Current Topics in Microbiology and Immunology |
| Volume: | 355 |
| ISSN: | 0070-217X |
| Publisher: | Springer Verlag |
| Date Published: | 2012-01-01 |
| Start Page: | 135 |
| End Page: | 169 |
| Language: | English |
| DOI: | 10.1007/82_2011_178 |
| PROVIDER: | scopus |
| PUBMED: | 22015553 |
| PMCID: | PMC3784987 |
| DOI/URL: | |
| Notes: | In "Therapeutic Kinase Inhibitors" (ISBN: 978-3-642-28295-9) -- "Export Date: 1 February 2013" - "CODEN: CTMIA" - "Source: Scopus" |
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